These projects are directed towards a greater understanding of the quarternary organization of plasma lipoproteins and of the function of the oligomeric species involved in the transport and metabolism of lipids in plasma. The apolipoprotein composition of plasma lipoproteins is viewed as the governing factor in directing lipoprotein metabolism. Specificity is believed to be related directly to apolipoprotein secondary, tertiary, and quaternary structure. Over the past several years we have quantitated the self- and mixed- associations of apolipoproteins A-I, A-II, C-I, C-III, E, and H. A knowledge of the equilibrium constants and stoichiometry for the specific complexes formed in plasma by apo-lipoproteins has allowed us to develop a framework for evaluating the role of apolipoproteins in controlling lipid metabolism. A knowledge of the specific complexes that exist in plasma is a prerequisite to our understanding of cholesterol and triglyceride transport. With this background we can predict the complexes that exist under a given set of experimental conditions. These studies have been extended recently to include lipoprotein lipase and hepatic lipase, two enzymes responsible for triglyceride hydrolysis. Over the past year we have evaluated quantitatively the molecular properties of bovine LPL and have established the experimental conditions for reproducibility of enzyme assays and long-term stability. The results of these studies have allowed us to design an isolation and purification scheme for LPL and HL that maximized yield of enzymic activity. We have developed a protocol for measuring the HL and LPL activity of post-heparin plasma for normal individuals and patients with disorders of lipid metabolism. Correlation of the lipid and apolipoprotein composition of these samples with HL and LPL enzymic activity should greatly increase our knowledge of lipid metabolism.